The basic objective of this research is the elucidation of the mechanism of neoplastic transformation of cells. Special emphasis will be placed on the biochemical analysis of the process of transformation in cells infected with avian sarcoma viruses. The studies will include the determination of subcellular localization of oncogene products, and identification of target host protein(s) whose phosphorylation is critical for cell transformation, and the characterization of changes in the expression of normal cellular genes in the process of transformation. Efforts will be made to identify cellular genes required for transformation. Analysis of the structure and functions of cellular and viral oncogene products and the conditions required for the conversion of the former to the latter will be investigated. As a part of this project we will analyze the mechanism of activation of the c-src protein by polyoma virus. The basis for tissue specific transformation by some oncogenic viruses will be explored. In order to understand the possible function of certain proto- oncogenes in normal cells, their expression will be analyzed in various cells at different developmental stages of animals.